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PubMed2001

Bone morphogenetic protein-7 modulates genes that maintain the vascular smooth muscle cell phenotype in culture.

BACKGROUND: The vasculature is an important component in the musculoskeletal system, and vascularization is a key event in the development of normal cartilage and bone formation. Blood vessels deliver nutrients, oxygen, and precursor cells to maintain the structural and functional integrity of joints and soft and hard tissues. Therefore, agents that help to inhibit proliferation and retain the phenotype of vascular smooth muscle cells (SMCs) are of critical importance. In this study, we examined the capacity of bone morphogenetic protein-7 (BMP-7) to inhibit the proliferation of SMCs and maintain their phenotype. METHODS: A thymidine-incorporation assay was used to monitor the proliferative activity of SMCs on stimulation with platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), agents known to be stimulatory for these cells. Reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to monitor the modulation of various genes and gene products. Immunolocalization of SMC specific markers was also performed. RESULTS: BMP-7 inhibited both serum-stimulated and growth factor-induced (PDGF-BB and TGF-beta1) SMC growth, as measured by 3H-thymidine uptake and cell number, in primary human aortic smooth muscle (HASM) cell cultures. The addition of BMP-7 stimulated the expression of developmentally regulated as well as SMC-specific markers, namely, Id-1 and Id-2, alpha-actin, and SMC-specific heavy-chain myosin, as examined by semiquantitative and quantitative RT-PCR and by Northern blot analysis. Additionally, BMP-7 exhibited anti-inflammatory activity by downregulating intercellular adhesion molecule-1 (ICAM-1) expression. The collagen type III/I ratio that becomes lower with the transdifferentiation of SMCs into myofibroblasts is maintained in BMP-7-treated cultures compared with untreated controls. Studies on the mechanism of action indicate that BMP-7 treatment induces cyclin-dependent kinase-2 inhibitor, p21, which was inhibited during PDGF-BB-induced proliferation of SMCs. Finally, BMP-7 upregulates the expression of the inhibitory Smads, Smad6 and Smad7, which are known to inhibit TGF-beta superfamily signaling. CONCLUSIONS: These results suggest that BMP-7 maintains the expression of the vascular SMC phenotype. Thus, BMP-7 may prevent vascular proliferative disorders and potentially could act as a palliative agent following damage to the vasculature. CLINICAL RELEVANCE: In musculoskeletal disorders in which the vasculature plays an important role, BMP-7 may be of benefit as an anti-inflammatory and anti-proliferative agent for vascular endothelium and help maintain vascular integrity.

Animals↗
PubMed2004

Improved access and targeting of musculoskeletal services in northwest Wales: targeted early access to musculoskeletal services (TEAMS) programme.

PROBLEM: The hospital based musculoskeletal service in northwest Wales was unable to cope with the demand for referrals from general practitioners. Waiting times were long, duplicate referrals to other departments were common, and general practitioners were reluctant to refer patients with common problems because of the perceived lack of service. Many referrals were made to the inappropriate specialty, especially orthopaedics. At least part of this problem was due to a lack of coordination between the four hospital departments providing musculoskeletal services and the emphasis on district general hospital based rather than community provision. DESIGN: Review over 18 months of impact of the targeted early access to musculoskeletal services (TEAMS) programme on accessibility to musculoskeletal services. SETTING: Northwest Wales. KEY MEASURES FOR IMPROVEMENT: Number of patients referred and seen with musculoskeletal problems, waiting times, number of duplicate referrals, and surgery conversion rates in orthopaedic clinics. STRATEGIES FOR CHANGE: Establishing with central clinical triage a common pathway for all musculoskeletal referrals so that patients attend the appropriate department. A back pain pathway led by extended scope physiotherapists was developed, and general practitioners with special interests and extended scope physiotherapists were trained to provide services for patients with uncomplicated musculoskeletal problems in the community. EFFECTS OF CHANGE: Over 18 months the number of referrals more than doubled. Despite this, waiting times for musculoskeletal services fell; this was noticeable for rheumatology and pain management. Duplicate referrals were abolished. Surgery conversion rates did not, however, change. Questionnaires from the clinics showed a high level of patient satisfaction. LESSONS LEARNT: Integration of hospital services that traditionally have worked in isolation can result in greatly improved access to musculoskeletal services. Community based multidisciplinary clinics run by specially trained general practitioners with special interests and extended scope physiotherapists are an effective way of managing patients with uncomplicated musculoskeletal problems and have been well received by patients and general practitioners. The huge unmet burden of need was reflected by the great increase in musculoskeletal referrals. Other approaches are needed to meet this, including better education of general practitioners and methods for identifying and modifying psychosocial risk factors for chronic pain at an early stage.

Health Services Accessibility↗
PubMed2003

Improved education in musculoskeletal conditions is necessary for all doctors.

It is likely that everyone will, at some time, suffer from a problem related to the musculoskeletal system, ranging from a very common problem such as osteoarthritis or back pain to severely disabling limb trauma or rheumatoid arthritis. Many musculoskeletal problems are chronic conditions. The most common symptoms are pain and disability, with an impact not only on individuals' quality of life but also, importantly, on people's ability to earn a living and be independent. It has been estimated that one in four consultations in primary care is caused by problems of the musculoskeletal system and that these conditions may account for up to 60% of all disability pensions. In contrast, teaching at undergraduate and graduate levels--and the resulting competence and confidence of many doctors--do not reflect the impact of these conditions on individuals and society. Many medical students do not have any clinical training in assessing patients with bone and joint problems. Under the umbrella of the Bone and Joint Decade 2000-2010, experts from all parts of the world with an interest in teaching have developed recommendations for an undergraduate curriculum to improve the teaching of musculoskeletal conditions in medical schools. The goal for each medical school should be a course in musculoskeletal medicine concentrating on clinical assessment, common outpatient musculoskeletal problems and recognition of emergencies. Improving competency in the management of musculoskeletal problems within primary care settings through improved education is the next aim, but there are needs for improvement for all professionals and at all levels within the health care system.

Curriculum↗
PubMed1997

Patients who develop inflammatory polyarthritis (IP) after immunization are clinically indistinguishable from other patients with IP.

Musculoskeletal symptoms may occur following various types of immunization, and it has also been suggested that, like infection, immunization may act as a trigger for rheumatoid arthritis (RA). A total of 48 of 898 (5.3%) patients with early inflammatory polyarthritis (IP) referred to the Norfolk Arthritis Register reported an immunization in the 6 weeks prior to symptom onset. There were no important clinical or demographic differences between the 48 immunized patients and 185 consecutive patients who did not report prior immunization. In addition, the frequencies of HLA-DRB1*01. *04 and the shared epitope in 33 of the immunized patients were similar to those in the 185 non-immunized patients and to those in 136 healthy controls. Further results from a case-control study suggest that the rate of immunization is higher amongst cases (5.5%) than age- and sex-matched controls (2.8%). In a small number of susceptible individuals, immunization may thus act as a trigger for RA.

Adolescent↗
PubMed1995

The development of rickets as a complication of chemotherapy for the treatment of Wilms' tumor.

Musculoskeletal complaints were the presenting symptoms in four of 44 children (9%) treated for relapsed Wilms' tumors with ifosfamide, a derivative of cyclophosphamide. Subsequent radiologic examination revealed rachitic bone and joint changes. A fifth child manifested clinical and radiographic signs of rickets after presenting with hypophosphatemia, hypouricemia, and glycosuria. Recognition of a potential drug-induced Fanconi syndrome is important when managing pediatric oncology patients previously treated with ifosfamide. Early replacement therapy is recommended when proximal renal tubular abnormalities are detected to help prevent and control the severe metabolic bone disease associated with the Fanconi syndrome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

An interactive graphics-based model of the lower extremity to study orthopaedic surgical procedures.

We have developed a model of the human lower extremity to study how surgical changes in musculoskeletal geometry and musculotendon parameters affect muscle force and its moment about the joints. The lines of action of 43 musculotendon actuators were defined based on their anatomical relationships to three-dimensional bone surface representations. A model for each actuator was formulated to compute its isometric force-length relation. The kinematics of the lower extremity were defined by modeling the hip, knee, ankle, subtalar, and metatarsophalangeal joints. Thus, the force and joint moment that each musculotendon actuator develops can be computed for any body position. The joint moments calculated with the model compare well with experimentally measured isometric joint moments. We developed a graphical interface to the model that allows the user to visualize the musculoskeletal geometry and to manipulate the model parameters to study the biomechanical consequences of orthopaedic surgical procedures. For example, tendon transfer and lengthening procedures can be simulated by adjusting the model parameters according to various surgical techniques. Results of the simulated surgeries can be analyzed quickly in terms of postsurgery muscle forces and other biomechanical variables. Just as interactive graphics have enhanced engineering design and analysis, we have found that graphics-based musculoskeletal models are effective tools for designing and analyzing surgical procedures.

Biomechanical Phenomena↗
PubMed1986

Clinical manifestations of Lyme disease.

Lyme disease typically begins with a unique skin lesion, erythema chronicum migrans (ECM) (stage 1). Patients with this lesion may also have headache, meningeal irritation, mild encephalopathy, multiple annular secondary lesions, malar or urticarial rash, generalized lymphadenopathy and splenomegaly, migratory musculoskeletal pain, hepatitis, sore throat, non-productive cough, conjunctivitis, periorbital edema, or testicular swelling. After a few weeks to months (stage 2), about 15% of patients develop frank neurologic abnormalities, including meningitis, encephalitis, cranial neuritis (including bilateral facial palsy), motor or sensory radiculoneuritis, mononeuritis multiplex, or myelitis. At this time, about 8% of patients develop cardiac involvement--AV block, acute myopericarditis, cardiomegaly, or pancarditis. Throughout this stage, many patients continue to experience migratory musculoskeletal pain in joints, tendons, bursae, muscle, or bone. Months to years after disease onset (stage 3), about 60% of patients develop frank arthritis, which may be intermittent or chronic. Recently evidence suggests that Lyme disease may also be associated with chronic neurologic or skin involvement. Thus, Lyme disease occurs in stages with different clinical manifestations at each stage, but the course of the illness in each patient is highly variable.

Borrelia↗
PubMed2005

Community Oriented Program for the Control of Rheumatic Diseases: studies of rheumatic diseases in the developing world.

PURPOSE OF REVIEW: The Community Orientated Program for the Control of Rheumatic Diseases (COPCORD) is based on collecting community data on rheumatic complaints and disability. After identifying significant problems, a search for disease risk factors is made, and control and treatment measures are recommended. This review covers the results of surveys in five countries-China, Brazil, Kuwait, Vietnam, and Australia-published in the last 18 months. RECENT FINDINGS: Musculoskeletal pain is a major health problem in all surveys undertaken in both developed and developing countries. Knee and low back pain are the most frequent complaints, and osteoarthritis is the most common arthritic disease identified, particularly affecting the knees. The prevalence of rheumatoid arthritis is generally lesser in these studies compared with published surveys of white patients. However, the prevalence of gout varied widely, possibly because of changes in lifestyle and racial factors. Septic arthritis and rheumatic fever were rarely seen except in an Australian aboriginal community, pointing to improvement in standards of living and health care, at least in the urban settings, according to the Vietnamese authors. SUMMARY: Population data are required on musculoskeletal complaints as a basis for decisions on health control and treatment programs. Surveys in five countries have identified the frequency of especially knee and low back pain, the prevalence of knee osteoarthritis, and the wide variability in the prevalence of gout, partly because of lifestyle and thus potentially correctable risk factors. Self-medication with potent pharmaceutical products in countries where doctors' prescriptions are not required is a recognizable health hazard.

Community Health Services↗
PubMed2000

A novel pharmacological approach of musculoskeletal losses associated with simulated microgravity.

Exposure to microgravity (weightlessness) is known to cause rapid bone and muscle losses. We have used the hind limb-suspended (HLS) rat model to simulate microgravity-induced musculoskeletal losses in order to assess resulting hormonal changes and to develop a novel pharmacological countermeasure. Previously, we demonstrated significant decreases in circulatory hormonal levels [serum thyroxin, 1,25(OH)2 vitamin D (p<0.05), and serum testosterone (p<0.001)] in HLS rats. Both thyroxin and 1,25(OH)2 vitamin D levels returned to normal soon after removal from HLS, while testosterone levels matched normal levels only after a further 3-4 weeks. However, even by day 42, bone mineral density (BMD) remained significantly lower, although serum hormones were back to normal. Because serum testosterone levels become undetectable in HLS rats, we hypothesized that the replacement of testosterone during HLS could prevent musculoskeletal losses. Based on these data, an intervention study was carried out to assess the efficacy of testosterone and synthetic anabolic steroid, nandrolone decanoate (ND), in prevention of weightlessness-induced musculoskeletal losses. HLS rats (control) had a significant reduction of muscle volume (42.9 -/+ 3.0, versus 56 -/+ 1.8 in ground control rats; p<0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 -/+ 2 cm(3) and 51.6 -/+ 1.2, respectively; a 63% improvement, p<0.05). Similarly, BMD of the placebo-treated HLS rats was significantly lower than that of ground control rats (0.416 -/+ 0.011 versus 0.354 -/+0.014, p<0.05), and testosterone and ND prevented this bone loss (0.404 -/+ 0.013 versus. 0.409 -/+ 0.011, respectively). These data suggest that both testosterone and ND therapy can minimize the musculoskeletal losses associated with exposure to simulated weightlessness. Experiments using the combination of bisphosphonate and testosterone demonstrated complete protection of both muscle and bone in these HLS rats. Therefore, considering that: 1) testosterone is anabolic to osteoblasts and muscle cells and also decreases the rate of bone turnover, 2) serum testosterone levels are markedly suppressed in simulated weightlessness, and 3) testosterone replacement therapy prevented musculoskeletal losses in HLS rats, we propose that the musculoskeletal losses observed in this animal model (i.e., simulated microgravity) are related to their testosterone deficiency. Since serum sex hormones levels are markedly reduced in this model of simulated microgravity, androgen replacement with a bisphosphonate seems to be a rational counter.

Journal Article↗
PubMed2006

Functional assessment of arthropathy--an international perspective.

Treatment of hemophilia aims to minimize structural damage to joints and maximize patients' functional independence and quality of life. From an orthopedic perspective, treatment efficacy can be judged by quantifying the extent of musculoskeletal damage. Joint scores--both clinical and radiologic--have traditionally been measured in patients with hemophilia. However, such scores may lack the sensitivity to detect early changes in the hemophilic joint, and this has prompted the development of more sensitive measures. In addition, scores based on the status of individual joints do not consider the impact of arthropathy on overall musculoskeletal function. It would prove valuable to understand the implications of small differences in clinical/radiologic scores in terms of overall musculoskeletal function and patients' quality of life. The development of functional scores such as the Functional Independence Score for Haemophilia (FISH) and the Haemophilia Activities List (HAL), along with the quality-of-life (QoL) measurement tools, have helped to provide a more comprehensive assessment of health in hemophilia. Such improved understanding should assist with the development of contextually relevant guidelines for the management of hemophilia.

Adolescent↗
PubMedDate not supplied

ICF Core Set for patients with musculoskeletal conditions in the acute hospital.

PURPOSE: The aim of this consensus process was to decide on a first version of the ICF Core Set for patients with musculoskeletal conditions in the acute hospital. METHODS: The ICF Core Set development involved a formal decision-making and consensus process integrating evidence gathered from preliminary studies including focus groups of health professionals, a systematic review of the literature and empiric data collection from patients. RESULTS: Twenty-one experts selected a total of 47 second-level ICF categories. The largest number of categories was selected from the ICF component Body Functions (17 categories or 36%). Nine (19%) of the categories were selected from the component Body Structures, 11 (23%) from the component Activities and Participation, and 10 (21%) from the component Environmental Factors. CONCLUSION: The Acute ICF Core Set for patients with musculoskeletal conditions provides all professionals with a clinical framework to comprehensively assess patients in the acute hospital. This first ICF Core Set will be further tested through empiric studies in German-speaking countries and internationally.

Activities of Daily Living↗
PubMed1998

Developmental effects of boric acid in rats related to maternal blood boron concentrations.

Timed-mated Sprague-Dawley rats (60/group) were exposed to boric acid (BA) from gestational days (gd) 0 to 20. BA added to the diet (0, 0.025, 0.050, 0.075, 0.1, or 0.2%) yielded boron (B) intakes of <0.35 (control), 3, 6, 10, 13, or 25 mg B/kg body wt/d. Approximately one-half of the dams/group were terminated on gd 20, maternal whole blood collected and frozen, and prenatal outcome (fetal growth, viability, and morphology) evaluated. Remaining dams received control diet beginning on gd 20, and litters were monitored throughout lactation. Blood samples were prepared by a high-temperature alkaline ashing method and analyzed for B by inductively coupled plasma (ICP) optical emission spectrometry. On gd 20, blood B concentrations of 1.27 +/- 0.298 and 1.53 +/- 0.546 microg B/g were associated with the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) (10 and 13 mg B/kg/d, respectively) for developmental toxicity. Developmental toxicity persisted postnatally only at 25 mg B/kg/d, a dose associated with >10-fold increase in maternal blood B (2.82 +/- 0.987 vs. 0.229 +/- 0.143 microg B/g for controls). Maternal blood B concentrations were: 1. Significantly elevated in all BA-exposed groups. 2. Positively correlated with maternal BA intake. 3. Inversely correlated with fetal body weight at doses above the NOAEL.

Animals↗
PubMed2004

The effects of ergonomics training on the knowledge, attitudes, and practices of teleworkers.

PROBLEM: The rapid growth of teleworking has raised several social and legal issues regarding an employer's responsibility for the safety of an employee's home office. In this paper, researchers discuss the need for safety training for teleworkers and the effectiveness of a home office ergonomics training program. METHOD: Study participants (N = 50) were randomly assigned into a treatment or control group. The treatment group completed the ergonomics training and a pre- and posttest. The control group completed the pre- and posttests without training. RESULTS: The study demonstrated the need for teleworker ergonomics training. More than 85% of participants had not received teleworker training before, and 44% had experienced pain or discomfort while teleworking. Participants who completed the training significantly improved their scores on knowledge, attitude, and practices subtests. In a follow-up survey, participants indicated that they had made ergonomic changes to their offices based on the training. Several participants indicated that the pain or discomfort that they had been experiencing was eliminated or reduced as a result of the training.

Analysis of Variance↗
PubMed2000

Shock accelerations and attenuation in downhill and level running.

OBJECTIVE: A study was conducted to investigate the possible effects of fatigue on the heel strike-initiated shock accelerations and on attenuation of these shocks along the body during eccentric muscle contractions. DESIGN: Level and decline running on a treadmill were used to acquire the experimental data on the foot strike-initiated shock accelerations. BACKGROUND: Eccentric contractions of the lower limb muscles in combination with shock generation and propagation during downhill running and muscle fatigue may diminish their ability to dissipate and attenuate loading on the system. METHODS: Fourteen young healthy males ran on a treadmill at a speed exceeding their anaerobic threshold by 5% for 30 min, as follows: (a) level running and (b) downhill running with a decline angle of -4 degrees. The foot strike-induced shock accelerations were recorded every five minutes on the tibial tuberosity and sacrum. Fatigue was monitored by means of the respiratory parameters. RESULTS: The downhill running related with eccentric muscle contractions was associated with increased shock propagation from the tibial tuberosity to the sacrum levels, even though fatigue did not develop. CONCLUSIONS: Shock propagation from the tibial tuberosity to the sacrum is augmented due to the eccentric action of the muscles, without metabolic fatigue development. RELEVANCE: Eccentric muscle contraction in downhill running reduces the musculoskeletal ability to attenuate the heel strike-induced shock waves. Knowledge about the effect of fatigue on the shock propagation between the shank and the sacrum levels may help in understanding the mechanism of stress fractures and joint damage.

Acceleration↗
PubMed2002

Identification of obstacles for chronic pain patients to return to work: evaluation of a questionnaire.

The Obstacles to Return-to-Work Questionnaire (ORQ) was developed and evaluated. A total of 154 patients with chronic musculoskeletal pain and prolonged work disability participated in the study. Factor analyses reduced the ORQ to 55 items grouped into 9 subscales. The subscales were named "Depression," "Pain intensity," "Difficulties at work return," "Physical workload and harmfulness," "Social support at work," "Worry due to sick leave," "Work satisfaction," "Family situation and support," and "Perceived prognosis of work return." The subscales showed satisfactory reliability. In order to determine predictive validity a discriminant analysis was conducted with sick leave 9 months after assessment as the outcome. This analysis indicated that the scales "Perceived prognosis of work return," "Social support at work," "Physical workload and harmfulness," "Depression," and "Pain intensity" could significantly predict sick leave and correctly classified 79% of the patients. The Multidimensional Pain Inventory and the Disability Rating Index could also significantly predict sick leave in this sample and correctly classified as many patients as the ORQ. However, these questionnaires do not include any work-oriented items and they had a lower specificity than the ORQ. This study suggests that patients' perceptions and beliefs about work and returning to work may be a significant hindrance for actual recovery.

Back Pain↗
PubMed1999

Diagnosing regional pain: the view from primary care.

There is a general lack of new evidence on which to base practical and useful diagnostic classifications of regional musculoskeletal pain for primary care. However, the'red flag' system, developed and now disseminated successfully in the management of low back pain, seems to be applicable to the initial management of other regional pain. In this scheme, signs and symptoms of serious disease are sought, and their presence is the indication for the investigation or referral of individual patients. In their absence, the low predictive value of many signs, tests and even diagnostic labels argues against their routine use in primary care. Simple decisions based on separation into articular versus non-articular, and acute versus chronic, are favoured by the most recent expert consensus statements. In addition, the presence or absence of more widespread pain, and of other non-specific features of chronic pain, is likely to be helpful in managing regional syndromes. Prospective studies of the prognostic value of symptoms, signs and diagnostic labels remain a research priority in this field.

Algorithms↗